The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Hesperidin prevents lipopolysaccharide-induced endotoxicity in rats.

CONTEXT Lipopolysaccharide (LPS) is a major trigger of septic shock resulting in multiple organ damage through excessive stimulation of the host's immune cells resulting in the release of cytokines. Previous studies have shown that hesperidin has several beneficial properties against inflammation and oxidative stress. OBJECTIVE The influence of hesperidin on endotoxemia, endothelial dysfunction, inflammation, and oxidative stress was investigated using a murine model of sepsis. MATERIALS AND METHODS Rats were pretreated for 15 d with three doses (50 mg/kg, 100 mg/kg, and 200 mg/kg) of hesperidin prior to LPS administration. Afterwards, the levels of biomarkers of endotoxemia, endothelial dysfunction, and oxidative stress were assessed. Reverse transcriptase PCR technique was used to assess the expression of hepatic proinflammatory cytokines. RESULTS Hesperidin pretreatment significantly (p < 0.05) reduced circulating endotoxin, as well as the levels of bactericidal permeability increasing protein and procalcitonin, and the associated endothelial dysfunction by reducing the levels of plasma soluble intercellular adhesion molecules 1 and inducible nitric oxide (iNO) synthase. There was also down-regulation of the expression of gene for interleukin 1α, interleukin 1β, interleukin 1 receptor, interleukin 6, and tumor necrosis factor α (TNFα) in the liver of rats treated with LPS as a result of hesperidin pretreatment. Hesperidin also showed anti-oxidative properties through the significant (p < 0.05) reduction of NO, hydroperoxides, and thiobarbituric acid reactive substances and increase of glutathione, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase in the organs. CONCLUSION Different doses of hesperidin can prevent endotoxemia-induced oxidative stress as well as inflammatory and endothelial perturbation in rats when administered for as few as 15 d before exposure to endotoxin

Stevioside modulates oxidative damage in the liver and kidney of high fat/low streptozocin diabetic rats

This study investigated the potential of stevioside to prevent oxidative DNA damage in the liver and kidney of type 2 diabetes mellitus (T2DM) using high fat-low streptozocin rat model. Rats were treated daily with 12.5, 25 and 50 mg/kg stevioside orally for 21 days. Levels of biomarkers of T2DM, lipid profile and oxidative stress were assayed spectrophotometrically. The DNA ladder assay method was used to assess DNA fragmentation in the liver and kidney while computational analysis was used to predict the mechanisms of antidiabetic properties of stevioside. Stevioside significantly (p < 0.05) decreased the levels of plasma glucose, insulin, dipeptidyl peptidase IV and activities of kidney angiotensin converting enzyme. Stevioside significantly reduced oxidative stress by decreasing the levels of lipid peroxidation and nitric oxide in the liver and kidney; thereby, reducing the extent of DNA fragmentation in the liver and kidney of the diabetic rats. The in silico analysis showed that the ability of stevioside to exert these effects is linked to its inhibition of beta-adrenergic receptor kinase and G-protein-coupled receptor kinase. The results of this study suggest that the prevention of DNA fragmentation may be an additional benefit of the use of stevioside in the management of T2DM

Gene Expression Profiling Analysis Reveals Putative Phytochemotherapeutic Target for Castration-Resistant Prostate Cancer.

Prostate cancer is the leading cause of cancer death among men globally, with castration development resistant contributing significantly to treatment failure and death. By analyzing the differentially expressed genes between castration-induced regression nadir and castration-resistant regrowth of the prostate, we identified soluble guanylate cyclase 1 subunit alpha as biologically significant to driving castration-resistant prostate cancer. A virtual screening of the modeled protein against 242 experimentally-validated anti-prostate cancer phytochemicals revealed potential drug inhibitors. Although, the identified four non-synonymous somatic point mutations of the human soluble guanylate cyclase 1 gene could alter its form and ligand binding ability, our analysis identified compounds that could effectively inhibit the mutants together with wild-type. Of the identified phytochemicals, (8'R)-neochrome and (8'S)-neochrome derived from the Spinach () showed the highest binding energies against the wild and mutant proteins. Our results identified the neochromes and other phytochemicals as leads in pharmacotherapy and as nutraceuticals in management and prevention of castration-resistance prostate cancers